5-nitrosimino-4-substituted-delta2-1,3,4-thiadiazoline-2-sulfonamides



S-NITROSIMINO- l-SU BSTlTUTED-fi-l i l-THA- DlAZOLlNE-Z-SULFONAMIDESRichard William Young, Riverside, and Melinda Jane Muller, Stamford,Conn., assignors to American Cyanamid Company, New York, N. Y., acorporation of Maine No Drawing. Application August 13, 1956 Serial No.603,841

12 Claims. (Cl. 260-3063) This invention relates to new organiccompounds and more particularly is concerned with novel S-nitrosimino-4-substituted-A -l,3,4-thiadiazoline-2-sulfonamides which may berepresented by the following general formula:

ONN- S /SOzNH wherein R is a lower alkyl radical, a monocyclic arylradical or a monocyclic aralky] radical. Suitable lower alkylsubstitutents are methyl, ethyl, propyl, isopropyl, butyl, pentyl, amyl,hexyl, etc.; suitable aralkyl substituents are benzyl, phenethyl,phenylpropyl, phenylbutyl, etc.; and suitable aryl substituents arephenyl and substituted phenyl, suitable substituents on the phenyl ringbeing Cl, --Br, l, -NO Cl-l O, and lower alkyl radicals containing fromi to 4 carbon atoms.

The compounds of this invention are excellent natriuretic agents, thatis agents which enhance the excretion of sodium in the urine withoutnecessarily changing the normal volume of urine excreted. The compoundsmay be administered orally and have been found to be effective indosages of from 5 mg. to 100 mg. per kilogram of body weight.

The novel compounds may be prepared by a reaction which is analogous todiazotization. in carrying out the process of this invention, the saltof an appropriate imino compound is reacted with nitrous acid in astrongly acid solution. The nitrous acid usually is generated in situ bythe addition of sodium nitrite to the suspension of the amine salt inexcess mineral acid. The reaction is preferably carried out attemperatures of around C., but the temperature may range from 0-30 C.since the final products are stable at room temperature as distinguishedfrom the conventional diazonium salts.

As the starting materials for preparation of the products of thisinvention, we use appropriate -imino-4- substituted-A1,3,4-thiadiazoline 2-sulfonamides, which compounds, in turn, areprepared by the acid hydrolysis of 5-acylimino-4-substituted-A l,3.4-thiadiazoline-Z-sulfonamides which are more particularly describedand claimed in the copending application of Young, Wood and Vaughan,Serial No. 492,297. filed March 4, 1955, now Patent No. 2,783,24l, andin the copending application of Young and Muller, Serial No. 560,866,filed January 23, 1956, now Patent No. 2,783,239.

The process by which the novel compounds of this invention may beprepared is illustrated schematically below using 5 imino-4-methyl-A-1.3,4-thiadiazoline-2-sulfonamide as an example of a suitable5-imino-4substituted- A -1,3,4-thiadiazoline-2-sulfonamide.

The invention will be described in greater detail in United StatesPatent Patented Jan. 21, 1958 ice there is added dropwise a solution of7.0 parts of sodium nitrite in 25 parts of water. The temperature ismaintained at 0 C. during the addition and the solution is will stirredfor two hours. A yellow solid forms which is removed by filtration.Concentration of the solution under an air jet gives an additionalquantity of solid. The total yield is l(l.8 parts (48% l. M. P. l48-l50dec. After several recrystallizations from alcohol (Norit A), 7.9parts 1. ol 5-nitrosmnno-4-methyl-A -1,3,4- thiadiazoline-Z-suIlonanudc.M. P. ISO-153 dec., is obtained.

Example 2 The procedure of the preceding example is repeated with thesole exception that an equivalent quantity of5-imino-4-ethyll,3.-l-thiadlazoline 2 sulfonamide is used. 5nitrosimino-4-ethyl-a -l,3.4-thiadiazole-2-sulfonamide is produced.

Example 3 The procedure of Example I is followed except that anequivalent quantity of S-imino-4-benzyl-A -l,3.4-thiadiazoline-Z-sulfonamide is used. 5-nitrosimino-4-benzyl--1,3,4-lhiadiazoltne-Z-sulfonamide is produced.

Example 4 The procedure of Example 1 is followed except that anequivalent quantity of 5-imino-4-phenyl-A-1,3,4-thiadiazoline-Z-sulfonamide is used. 5-nitrosimino4-phenyl- A-l.3.4-thiadiazoline-2-sulfonamide is produced.

Example 5 The procedure of Example 1 is followed except that anequivalent quantity of 5-imino-4-(m-tolyl)-A -l,3,4-thiadiazoline-Z-sult'onamide is used. 5-nitrosimino-4-(m-tolyU-y-l,3,4-thiadiazoline-Z-suIfonamide is produced.

Example 6 The procedure of Example 1 is followed except that anequivalent quantity of 5-imino-4-(p-chlorophenyD-M-i,3,4-thiadiazoline-2-sulfonamide is used. S-nitrosimino-4-(p-chIorophenyl)-n -1,3,4-thiadiazoline-2 sulfonamide is obtained.

Example 7 The procedure of Example 1 is followed with the exception thanan equivalent quantity of 5-imino-4-(p-acetomidophenyh-a-1,3,4-thiadiazoline 2 sulfonamide is used. 5nitrosimino-4-(p-acetamidophenyl)-A -1,3,4- thiadiazoline-Z-sulfonamideis obtained.

Example 8 The procedure of Example I is followed with the exception thatan equivalent quantity of 5-imino-4-(mmethoXyphenyD-A-1,3,4-thiadiazoline-2 sulfonamide is used. 5 nitrosimino4-(m-methoxyphenyl)-A -1,3,4- thiadiazoline-2-sulfonamide is obtained.

We claim:

1. 5 nitrosimino-4-substituted-A -1,3,4-thiadiazoline-2- sulfonamides ofthe formula:

ONN S/SOINHi wherein R is a member selected from the group consisting oflower alkyl, phenyl, halo-substituted phenyl,

1. 5 - NITROSIMINO-4-SUBSTITUTED-$2-1,3,4-THIADIAZOLINE-2SULFONAMIDES OFTHE FORMULA: